This is the renewal of the Bipolar Offspring Study (BIOS; NIMH #60952). In line with the current NIMH Strategic Plan, BIOS has been investigating the additive effects of dimensional/categorical psychopathology, circadian/sleep, cognitive, environmental, and biological factors associated with the development of mood disorders in offspring of parents with bipolar disorder (BD). BIOS recruited 509 offspring from BD parents (OBP) and 353 Offspring from Control Parents (OCP) and interviewed them blind to parental diagnoses with a comprehensive battery of instruments every other year since 2001, with 92% retention. Also, in a subsample of offspring, neuroimaging tests were performed. During the next funding period, most of the sample will be entering adulthood, a time when mood disorders peak, important life changes occur (e.g., marriage, work, children), and prefrontal systems reach final stages of development. We therefore propose to continue to study the BIOS sample to identify the clinical and psychosocial trajectories from childhood into adulthood, how these trajectories change during adulthood, and the prodromal symptoms of BD. In addition, in a BIOS subsample we aim to continue to identify RDoC domain-related biomarkers of neurodevelopmental trajectories underlying positive and negative emotion processing, reward, attentional control of emotion during emotion regulation, and executive function, and the demographic, familial, neural circuitry, and environmental factors that are predictors of psychopathology and resilience. To do this, we propose to: 1) continue following the entire BIOS sample; 2) perform a second scan and neurocognitive tests for the subsamples of OBP without BD (n=35) and OCP (n=35) with prior neuroimaging /neurocognitive data; 3) complete two scans and neurocognitive tests in 35 healthy youth offspring of healthy parents; and 4) for the first time in BIOS, include two scans and neurocognitive tests in 35 OBP who developed BD. We hypothesize that distinct RDoC domain-related patterns of function and white matter structure in emotion processing, reward, and emotion regulation neural circuitries are present in OBP, and to a lesser extent, in OCP. These patterns of neural circuitry function and structure, together with environmental factors (e.g., stressors), are associated with longitudinal trajectories manifested by increased dimensional psychopathology (e.g., subsyndromal mood symptoms, mood lability, sleep problems). The presence of dimensional psychopathology then increases the risk to develop mood and other disorders (e.g., anxiety, substance abuse), and psychosocial impairment. Recurrent subsyndromal manic and depressive episodes, irritability, mood lability and/or sleep disturbances will specifically increae risk for BD. Using this framework, we propose to characterize the clinical and psychosocial functioning trajectories into adulthood and determine the specific neural circuitry and environmental factors associated with increased risk for psychopathology, especially BD, and factors associated with resilience. Such findings will facilitate prompt diagnosis and intervention thus preventing, or at least ameliorating, the negative effects of BD in youth.